Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Canine Babesiosis Caused by Large Babesia Species: Global Prevalence and Risk Factors-A Review.

Canine babesiosis is a disease caused by protozoan pathogens belonging to the genus Babesia. Four species of large Babesia cause canine babesiosis (B. canis, B. rossi, B. vogeli, and the informally named B. coco). Although canine babesiosis has a worldwide distribution, different species occur in specific regions: B. rossi in sub-Saharan Africa, B. canis in Europe and Asia, and B. coco in the Eastern Atlantic United States, while B. vogeli occurs in Africa, southern parts of Europe and Asia, northern Australia, southern regions of North America, and in South America. B. vogeli is the most prevalent large Babesia species globally. This results from its wide range of monotropic vector species, the mild or subclinical nature of infections, and likely the longest evolutionary association with dogs. The most important risk factors for infection by large Babesia spp. include living in rural areas, kennels or animal shelters, or regions endemic for the infection, the season of the year (which is associated with increased tick activity), infestation with ticks, and lack of treatment with acaricides.

Disorders in Blood Circulation As a Probable Cause of Death in Dogs Infected with Babesia Canis.

INTRODUCTION: The purpose of the study was to investigate post-mortem changes in dogs infected with Babesia canis and to establish the probable cause of death of the affected animals. MATERIAL AND METHODS: Cadavers of six dogs that did not survive babesiosis were collected. Necropsies were performed and samples of various organs were collected for histological examination. RESULTS: Necropsies and histological examinations revealed congestion and oedemata in various organs. Most of the dogs had ascites, hydrothorax or hydropericardium, pulmonary oedema, pulmonary, renal, hepatic, and cerebral congestion, and necrosis of cardiomyocytes. CONCLUSION: These results suggested disorders in blood circulation as the most probable cause of death. However, the pulmonary inflammatory response and cerebral babesiosis observed in some of these dogs could also be considered possible causes of death. This study also showed a possible role for renal congestion in the development of renal hypoxia and azotaemia in canine babesiosis.

The Role of Interaction between Mitochondria and the Extracellular Matrix in the Development of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a condition which affects mainly older adults, that suggests mitochondrial dysfunction and oxidative stress, which follow cells senescence, and might contribute to the disease onset. We have assumed pathogenesis associated with crosstalk between the extracellular matrix (ECM) and mitochondria, mainly based on mitochondrial equilibrium impairment consisting of (1) tyrosine kinases and serine-threonine kinase (TKs and ST-Ks) activation via cytokines, (2) mitochondrial electron transport chain dysfunction and in consequence electrons leak with lower ATP synthesis, (3) the activation of latent TGF-ß via αVß6 integrin, (4) tensions transduction via α2ß1 integrin, (5) inefficient mitophagy, and (6) stress inhibited biogenesis. Mitochondria dysfunction influences ECM composition and vice versa. Damaged mitochondria release mitochondrial reactive oxygen species (mtROS) and the mitochondrial DNA (mtDNA) to the microenvironment. Therefore, airway epithelial cells (AECs) undergo transition and secrete cytokines. Described factors initiate an inflammatory process with immunological enhancement. In consequence, local fibroblasts exposed to harmful conditions transform into myofibroblasts, produce ECM, and induce progression of fibrosis. In our review, we summarize numerous aspects of mitochondrial pathobiology, which seem to be involved in the pathogenesis of lung fibrosis. In addition, an increasing body of evidence suggests considering crosstalk between the ECM and mitochondria in this context. Moreover, mitochondria and ECM seem to be important players in the antifibrotic treatment of IPF.

Gender differences in health-related quality of life measured by the Sarcoidosis Health Questionnaire.

Sarcoidosis is granulomatous disease, which complex etiology is yet to be fully discovered. In the majority of cases its course is self-limiting. However it can have different clinical manifestations and can be debilitating condition with great impact on health-related quality of life (HRQL). The aim of our study was to assess if there are any differences in HRQL dependent to gender. We examined a group of 33 males and 42 females (with no differences in mean age, disease activity, TLCO, FEV1, FVC, FEV1/FVC) with a use of Sarcoidosis Health Questionnaire. We revealed lower total and daily functioning score in female group. Further analyses stratified by sex and activity of the disease presented many significant differences between the groups, revealing important issues for the discussion about gender specific differences in the HRQL of patients with sarcoidosis. In spite of clinical presentation may be similar, expectations and main concerns of sarcoidosis patient can vary between females and males. Therefore, it appears that in terms of education and symptomatic treatment accents should be put differently depending on the gender of the patient. Our results may also point to a need for more gender-oriented patient-physician communication which could enable better understanding, potentially improve adherence to therapy and decrease the risk of possible complications.

The prognostic value of fixed time and self-paced walking tests in patients diagnosed with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia that has an unknown etiology. The natural history of the disease is characterized by a progressive decline in pulmonary function and overall health and well-being. The median survival time is between 2-3 years; however, the disease course is variable and unpredictable. The twelve-minute walking test (12MWT) and six-minute walking test (6MWT) are two fixed time tests that are commonly used in clinical practice. Our short and clinically oriented narrative review attempted to summarize current evidence supporting the use of fixed time, self-paced walking tests in predicting the outcome of patients diagnosed with IPF. A number of studies have justified that the 6MWT is a simple, cost-effective, well documented, fixed time, and self-paced walking test which is a valid and reliable measure of disease status and can also be used as a prognostic tool in patients with IPF. However, there is a need for dedicated and validated reference equations for this population of patients. It is also necessary to fill the knowledge gap about the role of the 12MWT. We hypothesize that it would be useful in evaluating patients that are in the early stages of the disease.

Eosinopenia and neutrophil-to-lymphocyte count ratio as prognostic factors in exacerbation of COPD.

Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPDs) are one of the most important clinical aspects of the disease, and when requiring hospital admission, they significantly contribute to mortality among COPD patients. Our aim was to assess the role of eosinopenia and neutrophil-to-lymphocyte count (NLR) as markers of in-hospital mortality and length of hospitalization (LoH) among patients with ECOPD requiring hospitalization. We included 275 patients. Eosinopenia was associated with in-hospital deaths only when coexisted with lymphocytopenia, with the specificity of 84.4% (95% CI 79.6-88.6%) and the sensitivity of 100% (95% CI 35.9-100%). Also, survivors presented longer LoH (P < 0.0001). NLR ≥ 13.2 predicted in-hospital death with the sensitivity of 100% (95% CI 35.9-100%) and specificity of 92.6% (95% CI 88.8-95.4%), however, comparison of LoH among survivors did not reach statistical significance (P = 0.05). Additionally, when we assessed the presence of coexistence of eosinopenia and lymphocytopenia first, and then apply NLR, sensitivity and specificity in prediction of in-hospital death was 100% (95% CI 35.9-100) and 93.7% (95% CI 90.1-96.3), respectively. Moreover, among survivors, the occurrence of such pattern was associated with significantly longer LoH: 11 (7-14) vs 7 (5-10) days (P = 0.01). The best profile of sensitivity and specificity in the prediction of in-hospital mortality in ECOPD can be obtained by combined analysis of coexistence of eosinopenia and lymphocytopenia with elevated NLR. The occurrence of a such pattern is also associated with significantly longer LoH among survivors.

Prevalence of anthelmintic resistance of gastrointestinal nematodes in Polish goat herds assessed by the larval development test.

BACKGROUND: Helminthic infections, in particular those caused by gastrointestinal nematodes (GIN), are found worldwide and are among the most economically important diseases of goats. Anthelmintic resistance (AR) in GIN of goats is currently present worldwide, and single- or multidrug resistant species are widespread. The aim of this study was to determine the prevalence of AR to benzimidazoles (BZ), macrocyclic lactones (ML) and imidazothiazoles represented by levamisole (LEV) in the Polish goat herds by using an in vitro larval development test, which is useful especially in large-scale epidemiological surveys. RESULTS: This cross-sectional study was conducted from September 2018 to June 2019 and enrolled 42 dairy goat herds scattered over the entire country. The most commonly used anthelmintic class in goat herds in Poland were BZ (92%), followed by ML (85%) and LEV (13%). BZ-resistant GIN populations were found in 37 herds (88%, CI 95%: 75 to 95%), ML-resistant GIN populations in 40 herds (95%, CI 95, 84 to 99%), and LEV-resistant GIN populations in 5 herds (12%, CI 95%: 5 to 25%). Multidrug resistance involving all three anthelmintic classes was found in 5 herds (12%, CI 95, 5 to 25%). Based on the morphological features of stage 3 larvae the main resistant GIN turned out to be Haemonchus contortus and Trichostrongylus spp. The use of BZ and frequency of anthelmintic treatments were significantly related to the presence of AR to BZ in Polish goat herds. CONCLUSIONS: This cross-sectional study demonstrates the existence of AR to BZ, ML and LEV on Polish goat farms. Resistance to BZ and ML is widespread, while AR to LEV is currently at a low level. A considerable proportion of herds harbours multidrug resistant GIN, which requires further consideration. An effective anthelmintic treatment strategy, reasonable preventive measures and better understanding of the resistance-related management practices by farmers and veterinarians may delay further development of AR.

Molecular identification of tapeworms from Konik Polski horses from Biebrza National Park.

Tapeworm infections in Konik Polski horses from Biebrza National Park were investigated in this study. Faecal samples were collected 10 times: in 2012 - 1 time, in 2013 - 4 times, in 2014 - 4 times and in 2015 - 1 time. In total, 162 faecal samples were collected and tested. Faecal egg counts (FECs) method was used in the study. Positive samples with cestode eggs were noted only twice - in October 2012 and December 2013 in two adult mares (9 and 11 years old). The determined prevalence was surprisingly low comparing to other studies, 4.3% in October 2013 and 28.5% in December 2013. Parasite genomic DNA was isolated from posterior proglottids of tapeworms found in horse faeces after deworming, PCR technique was applied in order to determine the species of these tapeworms. No specific products were obtained using primers specific to rDNA sequence, whereas, a 620 bp fragment encoding mitochondrial cytochrome oxidase I (COI) was amplified and sequenced. Nucleotide sequence analysis revealed a 100% homology to a corresponding fragment form Anoplocephala perfoliata tapeworm originating from a horse from the Czech Republic. To our knowledge this is the first report applying molecular techniques to tapeworm identification in Konik Polski horses.

The role of bronchoscopy in diagnosis of chronic cough in adults: a retrospective single-center study.

INTRODUCTION: Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional testing of samples collected during FOB in the differential diagnosis of chronic cough in adults. MATERIAL AND METHODS: This was a single-center retrospective study. Out of 7115 conventional white light FOB examinations, we finally selected 198 with cough as the only indication. RESULTS: In 40.9% of bronchoscopic examinations, no visible cause of cough was found. Visual signs of chronic bronchitis (CB) were detected in 57.6% of reports. Only in 3 cases (1.5%) bronchoscopy revealed a potential cause of chronic cough other than CB. Mycobacterium tuberculosis or other mycobacteria were spotted in none of the samples. In 91.1% of bronchoalveolar lavage (BAL) cytologic examinations, at least one cell count abnormality was detected, but only in case of increased percentage of eosinophils, it might be considered clinically relevant. In 53% of bacteriological culture results, at least one potentially pathogenic bacterium was isolated. CONCLUSIONS: The present study results strengthen the evidence that FOB combined with additional testing of airway specimens obtained during FOB is not a powerful tool in the differential diagnosis of chronic cough, and FOB as a diagnostic tool may be overused. The appropriate timing and decision regarding referral for FOB and additional testing of achieved material requires careful clinical consideration.

More than a Genetic Code: Epigenetics of Lung Fibrosis.

At the end of the last century, genetic studies reported that genetic information is not transmitted solely by DNA, but is also transmitted by other mechanisms, named as epigenetics. The well-described epigenetic mechanisms include DNA methylation, biochemical modifications of histones, and microRNAs. The role of altered epigenetics in the biology of various fibrotic diseases is well-established, and recent advances demonstrate its importance in the pathogenesis of pulmonary fibrosis-predominantly referring to idiopathic pulmonary fibrosis, the most lethal of the interstitial lung diseases. The deficiency in effective medications suggests an urgent need to better understand the underlying pathobiology. This review summarizes the current knowledge concerning epigenetic changes in pulmonary fibrosis and associations of these changes with several cellular pathways of known significance in its pathogenesis. It also designates the most promising substances for further research that may bring us closer to new therapeutic options.

Ageing, sex, obesity, smoking and COVID-19 - truths, myths and speculations.

In early December 2019, in the city of Wuhan in Hubei Province, China, the first infections by a novel coronavirus were reported. Since then, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been spreading to other cities and countries becoming the global emerging epidemiological issue and quickly reaching the status of a pandemic. Multiple risk factors of disease severity and mortality have been identified so far. These include old age, male sex, smoking, and obesity. This concise narrative review highlights the important role of these factors in the pathobiology and clinical landscape of Coronavirus Disease 2019 (COVID-19). We especially focused on their significant role in disease severity and mortality. However, in spite of intensive research, most of the presented pieces of evidence are weak and need further verification.

The first report of multidrug resistance in gastrointestinal nematodes in goat population in Poland.

BACKGROUND: Prophylactic anthelmintic treatment with one of three basic classes of anthelmintics (benzimidazoles, macrocyclic lactones and imidazothiazoles) is still the mainstay of control of gastrointestinal nematode infections in small ruminants worldwide. As a consequence, anthelmintic resistance is a serious threat to small ruminant health and production. While the resistance to one class of anthelmintics has already been reported in most of countries, the newly-emerging problem is the resistance to two or even all of classes referred to as multidrug resistance. This study aimed to evidence the presence of multidrug resistance of gastrointestinal nematodes in goats in Poland. RESULTS: The combination of one in vivo method (fecal egg count reduction test) and two in vitro methods (egg hatch test and larval development test) performed in two goat herds in the southern Poland showed the presence of gastrointestinal nematodes resistant to fenbendazole and ivermectin in both herds. Moreover, in one herd it revealed the development of resistance to the last effective anthelmintic, levamisole, in response to one-year intensive use. Haemonchus contortus was the most prevalent gastrointestinal nematode in samples in which resistance to benzimidazoles and ivermectin was found, whereas Trichostrongylus colubriformis predominated when resistance to levamisole was observed. CONCLUSION: This study shows for the first time that multidrug resistance of gastrointestinal nematodes to three basic classes of anthelmintics is already present in goat population in Poland. Moreover, it may indicate that different species or genera of gastrointestinal nematodes are responsible for the resistance to specific anthelmintics.

Assessment of microvascular function in vivo using flow mediated skin fluorescence (FMSF) in patients with obstructive lung diseases: A preliminary study.

BACKGROUND: Cardiovascular diseases play an important role in the morbidity and mortality of patients with obstructive lung diseases. Impaired vascular endothelial function seems to be a key element linking obstructive lung disease and cardiovascular disease. Recently developed technique named flow mediated skin fluorescence (FMSF) is a novel, non-invasive tool to study microvascular function. METHODS: Total of 69 volunteers including 26 patients with chronic obstructive pulmonary disease (COPD), 23 patients with asthma and 20 healthy subjects underwent microvascular function assessments using FMSF. FMSF assessments were composed of measurements of reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence intensity signal during brachial artery occlusion - ischemic response (IRmax) and immediately after release of occlusion - hyperemic response (HRmax). Associations of microvascular function with clinical and biochemical characteristics of studied subjects were also evaluated. RESULTS: The median value of IRmax was significantly lower in COPD subjects (2.4 [1.0-6.7] %) compared with healthy subjects (9.6 [3.7-13.5] %; p < 0.01). The mean value of HRmax was also significantly reduced in COPD subjects (9.7 (4.5) %) compared with both asthma subjects (12.1 (3.5) %; p < 0.05) and healthy control subjects (13.4 (2.9) %; p < 0.01). CONCLUSIONS: The FMSF technique makes it possible to identify impairments of the microvascular function in patients with COPD, but not in asthma patients. These exploratory findings require further validation in a larger patients cohort.

Sarcoidosis and calcium homeostasis disturbances-Do we know where we stand?

The majority of cases involving hypercalcemia in the setting of sarcoidosis are explained by the overproduction of calcitriol by activated macrophages. Vitamin D takes part in the regulation of granuloma formation. However, using vitamin D metabolites to assess the activity of the disease is still problematic, and its usefulness is disputable. In some cases, though, a calcium metabolism disorder could be a valuable tool (i.e. as a marker of extrathoracic sarcoidosis). Although sarcoidosis does not cause a decrease in bone mineral density, increased incidence of vertebral deformities is noted. Despite increasing knowledge about calcium homeostasis disorders in patients with sarcoidosis, there is still a need for clear guidelines regarding calcium and vitamin D supplementation in these patients.

Hyponatraemia and Syndrome of Inappropriate Antidiuretic Hormone Secretion in Non-azotaemic Dogs with Babesiosis Associated with Decreased Arterial Blood Pressure.

INTRODUCTION: A previous study on canine babesiosis showed low serum tonicity in affected dogs, which may result from syndrome of inappropriate antidiuretic hormone secretion (SIADH). This endocrine disorder was recognised in human malaria which is considered a disease with similar pathogenesis to canine babesiosis. The aim of this study was to investigate the occurrence of SIADH in babesiosis-afflicted dogs. MATERIAL AND METHODS: Serum and urinary sodium and urine specific gravity (USG) were determined in dogs with babesiosis. Mean arterial pressure (MAP) was measured at the beginning of the clinical examination. Serum tonicity and osmolality were calculated. Correlations were calculated between MAP and serum and urinary sodium concentrations, USG, serum tonicity, and calculated serum osmolality. RESULTS: Statistically significant correlations were observed between MAP and tonicity, calculated osmolality, USG, and serum and urinary sodium concentrations in non-azotaemic dogs. In three non-azotaemic dogs SIADH was recognised. CONCLUSION: SIADH develops in non-azotaemic dogs with babesiosis. It is probably associated with decreased blood pressure in infected dogs. Thus, it seems that in fact it may be appropriate vasopressin secretion in canine babesiosis as a protective mechanism in hypotension which leads to hypoxia and renal failure in affected dogs.

Epithelial Alarmins in Serum and Exhaled Breath in Patients with Idiopathic Pulmonary Fibrosis: A Prospective One-Year Follow-Up Cohort Study.

BACKGROUND: Recently, epithelial alarmins have been shown to play important roles in non-allergen driven respiratory diseases like idiopathic pulmonary fibrosis (IPF). Little is known about the expression of the epithelial alarmins in IPF. METHODS: This study aimed to prospectively examine interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in the serum and exhaled breath condensate (EBC) in patients with IPF before and after one-year of antifibrotic treatment. A total of 82 volunteers, including 52 patients diagnosed with IPF that qualified for antifibrotic therapy as well as 30 controls, were examined. All study participants underwent baseline peripheral blood and EBC sampling. In 35 out of 52 IPF subjects, a follow-up sampling was performed after 12 months of antifibrotic treatment. Concentrations of alarmins in the serum and EBC were evaluated by means of ELISA. RESULTS: Baseline TSLP concentrations were significantly elevated in patients with IPF compared to controls both in the serum (p < 0.05) and EBC (p < 0.0001). Baseline IL-25 and IL-33 serum and EBC levels did not differ significantly between IPF subjects and controls. Prospective analysis of changes in the epithelial alarmin levels showed significantly decreased IL-25 and TSLP EBC concentrations after 12 months of antifibrotic treatment (p < 0.05), which was observed in the subgroup of IPF patients treated with pirfenidone, but not in those treated with nintedanib. In stable patients with IPF over a study period (absolute forced vital capacity (FVC) % of predicted decline/year ≤ 5%, n = 25), a significant decrease in the EBC levels of both IL-25 and TSLP after 12 months of antifibrotic treatment was noted (p < 0.05), whereas, in progressor IPF patients (absolute FVC % of predicted decline/year > 5%, n = 10), a significant decrease was noted in the IL-25 EBC levels only (p < 0.05). CONCLUSIONS: Elevated TSLP levels in patients with IPF and their significant decrease in the lung compartment during antifibrotic therapy in stable patients with IPF, but not in progressors, support its significant contribution to pro-fibrotic type 2 immune responses in IPF. Noted changes in the epithelial alarmins concentration in the lung compartment during pirfenidone therapy may suggest its possible interaction with epithelial alarmins pathways in IPF.

Telomere Abnormalities in the Pathobiology of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) occurs primarily in older adults and the incidence is clearly associated with aging. This disease seems to be associated with several hallmarks of aging, including telomere attrition and cellular senescence. Increasing evidence suggests that abnormalities involving telomeres and their proteome play a significant role in the pathobiology of IPF. The aim of this study is to summarize present knowledge in the field, as well as to discuss its possible clinical implications. Numerous mutations in genes associated with telomere functioning were studied in the context of IPF, mainly for Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC). Such mutations may lead to telomere shortening, which seems to increase the risk of IPF, negatively influence disease progression, and contribute to worse prognosis after lung transplantation. Some evidence indicates the possibility for the use of telomerase activators as potential therapeutic agents in pulmonary fibrosis. To sum up, increasing evidence suggests the role of telomere abnormalities in the pathobiology of IPF, natural history and prognosis of the disease. There are also possibilities for telomerase targeting in the potential development of new treatment agents. However, all these aspects require further research.

Overexpression of chitotriosidase and YKL-40 in peripheral blood and sputum of healthy smokers and patients with chronic obstructive pulmonary disease.

Background: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown. Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD. Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated. Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P<0.05 and P<0.01, respectively). A similar pattern was observed for PBMC chitotriosidase mRNA expression (P<0.001). YKL-40 serum concentrations were elevated in healthy smokers and COPD subjects compared to healthy never-smokers (P<0.001 and P<0.01, respectively). In sputum, YKL-40 levels were increased in COPD compared to healthy never-smokers (P<0.01). PBMC YKL-40 mRNA expression was increased in COPD and healthy smokers compared to healthy never-smokers (P<0.0001). No associations were found between chitotriosidase or YKL-40 peripheral blood levels and sputum levels. Conclusions: Our results demonstrate that chitotriosidase and YKL-40 are overexpressed in peripheral blood and airways in both healthy smokers and COPD subjects which may indicate smoking-related activation of macrophages, neutrophils, and epithelial cells.

Epithelial alarmin levels in exhaled breath condensate in patients with idiopathic pulmonary fibrosis: A pilot study.

INTRODUCTION: Interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP) are epithelial alarmins involved in innate immune responses and have been shown to play an important role in chronic lung diseases. No data are available regarding their levels in exhaled breath condensate (EBC) in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To examine IL-25, IL-33 and TSLP levels in the EBC obtained from patients with IPF and compare them to those in healthy controls, patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: Twenty-three patients with asthma, 25 patients with COPD, 15 patients with IPF and 16 healthy controls were studied. Concentrations of alarmins in the EBC were evaluated by means of ELISA. RESULTS: IL-25 EBC levels were numerically lowest in IPF (25.33 ± 8.84 pg/ml). However, they did not differ significantly from healthy subjects (43.18 ± 5.53 pg/ml), but were significantly lower compared to asthma (72.07 ± 6.03 pg/ml; P < .001). IL-33 EBC levels were significantly increased in IPF (3.41 ± 0.55 pg/ml) compared to healthy controls (1.20 ± 0.60 pg/ml; P < .01) but did not differ from asthma (3.68 pg/ml) and COPD levels (2.47 ± 0.34 pg/ml). There were significant correlations between IL-33 EBC levels and lung diffusion capacity of carbon monoxide (DLco ) absolute (r = .63; P < .05) and % of predicted values (r = .67; P < .01) as well as with time since diagnosis (r = -.59; P < .05) in IPF subjects. TSLP was undetectable in examined samples. CONCLUSION: IL-25 and IL-33 are detectable in the EBC obtained from IPF subjects. Increased levels of IL-33 compared to healthy controls indicate its possible role in the pathobiology of IPF.